The mechanisms underlying the process of conversion of dividing undifferentiated mouse neuroblastoma cells to nondividing differentiated cells will be studied. A variety of agents and conditions that stimulate this conversion will be examined, including serum-free media, cyclic AMP, dibutyryl cyclic AMP, phosphodiesterase inhibitors, sodium butyrate and the prostaglandin PGE1. The degree of differentiation will be assessed by measuring decrease in cell division, increase in neuronal functions, formation of processes and tumorgenicity of the cells. The neuronal properties of the two forms of the cells will be compared under the various differentiating conditions, especially with regard to neurotransmitter uptake and storage. The effects of cytotoxic drugs that have selective effects on nerve tissue will be studied on both forms of neuroblastoma cells, both in culture and in tumor-bearing mice. Combinations of cytotoxic drugs and differentiating agents will also be studied. It is hoped that this research will contribute to eventually developing agents having selective cytotoxic actions on neuroblastoma cells.